What Do We Know about Anthracofibrosis? A Literature Review.

Recently, the significance of anthracosis in the tracheobronchial tree, lung parenchyma, and even non-respiratory organs has been postulated and discussed in association with other diseases, especially tuberculosis. We reviewed the current literature by using the following key words in Medline/PubMed, Embase, and Google Scholar databases: anthracosis, anthracofibrosis, anthracotic bronchitis, biomass fuels, and mixed-dust pneumoconiosis. The bibliographies of eligible papers were also reviewed for further relevant articles. A total of 37 studies were assessed. The content of these studies was then divided into specific categories. Considering the pathogenesis, along with histopathological, radiological, and bronchoscopic results regarding anthracotic lesions, we suggest these findings be defined as "ANTHRACOSIS SYNDROME". For the first time, we describe a syndrome involving black pigmentation, which was previously thought to involve only the tracheobronchial tree. Until recently, it was not considered to be a single syndrome with different sites of involvement.


INTRODUCTION
Anthracosis is a term used to describe black pigmentation of the tracheobronchial tree involving both mucosal and submucosal layers and lung parenchyma, or black pigmentation in macrophages caused by the deposit of carbon, silica, and quartz particles (1)(2)(3)(4). Thus, it is not a disorder, per se (5). It was first defined by Cohen in 1951 (6). If anthracosis is associated with mucosal proliferation resulting in luminal obliteration and/or obstruction, it refers to the condition anthracofibrosis, which was first described by Chung et al. in 1998 (7). There have been TANAFFOS other synonyms for these conditions, including anthracotic bronchitis, anthracostenosis that first used by Törün et al.(8) specifically for patients with a history of long-term exposure to biomass smoke (9), and bronchial anthracosis (10). Given the widespread clinical manifestations and the histopathological, radiological, and bronchoscopic findings discussed in this study, we assume that the black pigmentations would cause deposits to form in multiple organs. Thus, it is more appropriate to consider this condition "ANTHRACOSIS SYNDROME".
Anthracosis is an ancient disease, reported even in mummies (11). However, recently, there has been an interest in recognizing its clinical significance, as anthracosis is often an incidental finding during bronchoscopic evaluation of patients with non-specific clinical symptoms such as cough, dyspnea, phlegm, and wheezing (12). On the other hand, anthracofibrosis may be indicative of a chronic disease of both the tracheobronchial tree and lung (13).
Here, we reviewed the current information on anthracosis and anthracofibrosis, including epidemiology, etiology, pathogenesis, clinical manifestation, and natural course, associated conditions, mediastinal lymphadenopathy, cancer susceptibility, lung parenchymal involvement, bronchopneumonia susceptibility, other organ involvement, diagnosis method, and finally, prevention and treatment.
display symptoms (18,(23)(24)(25). In both Korean and Iranian rural homes, the kitchen is a place for cooking and heating using biomass fuels such as wood, leaves, and crop residues. In this setting, ventilation is almost always restricted to a single window on the roof, resulting in inadequate air circulation. This housing condition and lifestyle are often the same in studies reporting BAF in other countries (18). Previous studies have revealed that cooking smoke is associated with a higher risk of chronic lung diseases. Although there are limited data on patients with BAF in developed countries, some cases of BAF have been reported. These patients were immigrants to North America from developing countries such as India, where biomass fuel had been used (18,26,27).
A study published in 2010 reported that BAF with associated pulmonary tuberculosis (PTB) was common in immigrants to Canada from the Indian subcontinent (28). In this study involving 61 patients of foreign origin with PTB, 10 (16.7%) were diagnosed with BAF; nine of these patients were from the Indian subcontinent and one was from Vietnam. As with previous studies, the majority of patients were females, with a mean age of 69.8 ± 9.3 years (15).
These data suggest that most patients diagnosed with anthracotic bronchitis are non-smoking elderly women living in a rural setting who have had no relevant occupational history for anthracosis (29,30).

Etiology:
The main cause of anthracosis/anthracofibrosis is

Pathogenesis:
The exact pathogenesis of anthracofibrosis is still a mystery. There have been two hypotheses regarding clinical and histopathological findings. The first hypothesis is based on TB infection and explains the high coexistence of TB in anthracotic patients (2,16,31). The second theory was developed to describe why, in some studies, authors were unable to find any relation between TB and anthracofibrosis.
The first hypothesis theorizes that silica containing pigmentation causes alteration in the immune mechanisms of the lungs, making them prone to M. tuberculosis infection (43). Individuals with persistent long-term exposure to air pollutants, cigarette smoke, and biomass fuel smoke develop carbon and silica accumulation in their lymph nodes (44). If these lymph nodes become infected with M.
tuberculosis, they rupture into the adjoining tracheobronchial tree, leading to black pigmentation, subsequent inflammation and fibrosis (6,10, 45). In favor of this hypothesis is the fact that, in some studies, anthracotic patients receiving tuberculosis treatment clinically improved (7).
The second hypothesis theorizes that biomass fuels where there is a relatively lower clearance rate (48).
Deposited carbonaceous particles cause fibrosis of the bronchial wall or the surrounding interstitium, resulting in hypertrophy of the bronchial wall and narrowing of the bronchial lumina (18). It seems that neither of these hypotheses can explain every aspect of anthracofibrosis pathogenesis. Therefore, there may be two possible causes of the same entity (16).
The most common symptom associated with pulmonary auscultation in patients with anthracosis is wheezing (7); rales or decreased breathing sounds are noted less frequently (32). Normal physical examination is noted in some cases but the exact prevalence is unclear (19). One possible explanation for this variation may be the association of anthracofibrosis with other diseases, resulting in altered clinical features for some patients.

Natural course:
The course of anthracofibrosis is chronic, and it is commonly misdiagnosed as chronic bronchitis. Most patients with bronchial anthracotic lesions had a stationary and inactive course that might be interrupted by acute attacks (20).

Associated conditions:
Although some studies report a strong association between anthracofibrosis and TB, Park et al. (41) does not.
We assume this discordance originates from the

Bronchopneumonia susceptibility:
It could be that bronchopneumonia is prevalent in anthracotic patients due to bronchial narrowing, which leads to poor drainage of secretions and predisposes the patient to recurrent infections (68), but Singh et al. did not find a significant association between bronchopneumonia and anthracosis in their study population (10).
On the other hand, Cho et al. reported a high incidence of pneumonia in up to 40% of anthracotic patients and opined that the location of pneumonic consolidation on a CXR is often consistent with lobes that have bronchial narrowing. Thus, bronchial anthracofibrosis may be a major risk factor for pneumonia (69).

Additional organ involvement:
Anthracosis may affect other organs in the body, as there are reports of liver and spleen involvement. As The diagnosis should be confirmed using histopathological evaluation(13).

Concomitant esophageal anthracosis:
Esophageal anthracosis is a rare disease. Yang et al.

Lung parenchymal involvement:
In some cases, anthracofibrosis may involve lung parenchyma with the same mechanism involving the bronchial tree.

Diagnosis:
The definitive diagnosis of anthracofibrosis is usually achieved during a bronchoscopic examination of patients with chronic cough, sputum, and dyspnea (9).
Pulmonologists should consider the possibility of this disease, especially in older, non-smoking women exposed to biomass combustion products. Sputum samples should be taken for acid-fast bacilli smear and culture, and, if TB is confirmed, the proper treatment with radiographic followup should be initiated (28).

Radiology:
Radiological sensitivity and 89% specificity. They also reported bronchial calcification as a useful finding, as it had an odds ratio of 9.4 for anthracofibrosis (13).
In this regard, the third most-common radiological finding in anthracosis/anthracofibrosis patients was a benign mass with or without calcification. Other radiological findings noted at a lower frequency included collapse, bronchial stenosis, and collapse consolidation (13). Another study from Iran by Amoli (20)

Fludeoxyglucose Positron Emission Tomography (FDG PET):
It has been reported that Positron Emission Tomography (PET) has greater than 90% sensitivity, but a specificity of only about 80% in diagnosing pulmonary pathology. Fludeoxyglucose (FDG) is a glucose analogue that is transported into both normal and malignant cells.

Diagnosis of TB in anthracosis patients:
Clinical symptoms such as cough, hemoptysis, and even radiological characteristics of tuberculosis such as

Prevention and Treatment:
There is no specific treatment for anthracofibrosis, and

Cases of misdiagnosed anthracotic lymph node with lung metastasis:
There were a few reports in the literature regarding the possible benign differential diagnosis of intrapulmonary round lesions, especially in patients with previous cancer history. This type of lesion has characteristic radiological features, including a sharp margin with a homogenous inner pattern. Here we represent two cases. These reports suggest that benign lesions such as anthracotic lymph nodes, although less common, should also be considered as differential diagnoses of intrapulmonary round lesions in patient with known preceding malignant disease. However, false positives of radiological modalities should be noted as well. Thus, histological assessment should be performed in order to decipher the appropriate treatment.

CONCLUSION
In light of our findings, it seems that previously known anthracotic pigmentation in the bronchial tree is a manifestation of a greater syndrome. This histopathological finding may be observed in other parts of both respiratory and non-respiratory organs sharing the same pathogenesis, leading to almost the same clinical picture. In this regard, we suggest that it is better to consider all different aspects of anthracosis as ANTHRACOSIS SYNDROME. This comprehensive attitude may be helpful to 1) better understand what we are dealing with, 2) estimate its importance, especially in association with TB, 3) find potential cancer susceptibility, and 4) provide rapid and safe treatment whenever indicated.